THU0013 Interaction between two common HLA antigens defines a subset of individuals at a very high risk for ankylosing spondylitis

Background Susceptibility to spondyloarthritis (SpA) is largely genetically determined. To understand increasingly complex genetic associations, one can look for interaction between genetic risk factors. Objectives In this study, we investigated interaction between common HLA class I risk antigens in ankylosing spondylitis (AS) the most typical form of SpA. Methods In 155 patients with AS and 5584 controls, common HLA class I antigens were analyzed for association with AS. Biologic interaction was analyzed by investigating whether the effects of the risk factors combined departed from additivity. Results Apart from an association with HLA-B27, we found an association between HLA-B60 and AS (OR 2,0; 95%CI 1.3-2.9; p With HLA-B27-/HLA-B60- AS patients as the reference, the relative risk (RR) for HLA-B27-/HLA-B60+ patients was 2.3 (CI 0.9-5.8). For HLA-B27+/HLA-B60- the RR was 66 (CI 40-111) but increased to 342 (CI 167- 703) in HLA-B27+/HLA-B60+ patients. For the interaction, the relative excess risk (RERI) was 310 (95% CI 130-490), the attributable proportion (AP) was 0.8 (CI 0.7-0.9), and the synergy index (S) 5.7 (CI 3.8 -8.5). The interaction was confirmed in an independent cohort. Conclusions We report a strong interaction between HLA-B60 and HLA-B27 in AS susceptibility. As a result, individuals with the HLA-B27+/HLA-B60+ genotype are at a very high risk of developing AS. Disclosure of Interest None Declared